| Expression pattern: |
UP |
| Associated gene: |
TCF4, CTNNB1 |
| Associated microRNA: |
miR-1276 |
| Biological function: |
promotes GC cell proliferation and tumorigenesis; inhibits apoptosis |
| Molecular mechanism: |
Nuclear circ_SMAD4 recruits TCF4 to enhance CTNNB1 transcription; cytoplasmic circ_SMAD4 acts as a miR-1276 sponge to prevent repression of CTNNB1 mRNA, activating the Wnt/beta-catenin pathway. |
| Biological pathway or process: |
Wnt/beta-catenin (promotes); proliferation (promotes); apoptosis (inhibits); ceRNA regulation (promotes) |
| Detected method: |
Q
M
|
| Validation methods: |
Microarray; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; Agarose gel electrophoresis assay; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; RNA Pull-Down; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; ChIP / ChIP-seq; Transfection; Colony Formation Assay; EdU Staining; Annexin V/PI Flow Cytometry; Western Blot; In Vivo Animal Model; IHC (Immunohistochemistry); Clinical Sample Validation; Survival Analysis |
| Clinical significance: |
high circ_SMAD4 level predicted dreadful survival in GC patients |
| Description: |
circ_SMAD4 (hsa_circ_0047718), derived from SMAD4, is up-regulated in gastric cancer and its high expression is associated with worse survival. It promotes GC proliferation and tumorigenesis by activating CTNNB1-dependent Wnt/beta-catenin signaling via recruiting TCF4 to enhance CTNNB1 transcription and sponging miR-1276 to relieve post-transcriptional repression of CTNNB1. |
| Confidence score: |
0.891 |